Ester reaction products of 1,4-Benzenedicarboxylic acid with C11-14 iso-alcohols, C13-rich

Endpoint summary

Key value for chemical safety assessment

Genetic toxicity in vitro

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (negative)

Additional information

Two genetox studies were located for the submission substance. In bacterial tests, the submission substance was not mutagenic in Salmonella strains tested in the presence or absence of metabolic activation. Similarly, the submission substance was not clatogenic in an in vitro mammalian cell chromosome aberration test.  Data on the analogous substance, Di(2-ethylhexyl)terephthalate (DEHT)was used as read-across to assess the genetic toxicity potential in an in vitro mammalian cell mutagenicity assay. The lack of a positive response in the cultures treated with DEHT at dose levels up to and slightly higher than the solubility limit of DEHT in the assay medium demonstrates that DEHT was not mutagenic in this test system. All studies were conducted in a manner similar or equivalent to currently established OECD guidelines. Based on these data, this substance is considered to be non-genotoxic and classification is not warranted. 

Short description of key information:

In vitro gene mutation in bacteria, 1 key study-Negative (equivalent or similar to OECD TG 471)

In vitro, gene mutation mammalian, 1 key study, read-across-Negative (equivalent or similar to OECD TG 476)

In vitro chromosome aberation test, 1 key study-negative (according to OECD 473)

Endpoint Conclusion: No adverse effect observed (negative)

Justification for classification or non-classification

All in vitro genetic toxicity studies (e.g. gene mutation in bacteria, cytogenicity in mammalian cells, and gene mutation in mammalian cells) showed negative results. Based on these results the submission substance is unlikely to be mutagenic and does not meet the criteria for classification as a genotoxin or a clastogen under the new Regulation (EC) 1272/2008 on classification, labeling, and packaging of substances and mixtures (CLP) or under the Directive 67/518/EEC for dangerous substances and Directive 1999/45/EC for preparations. 

Justification for Read-Across

For the purpose of this assessment, data for a lower molecular weight terephthalate, di(2-ethylhexyl) terephthalate (DEHT), was used be used as read-across. This read-across approach is based on the principle that substances of similar structure have similar toxicological properties and the premise that a narrow range of ester carbon numbers will produce trends in physicochemical, environmental and toxicological properties. Both the submission substance and DEHT are composed of a1,4-benzenedicarboxylic acid moiety with a branched alkyl alcohol attached to the acid units via an ester linkage (referred to as the alkyl side chains).The distinguishing feature between DEHT and the submission substance is in the alkyl side chains. DEHT has alkyl side chains with a 2-ethylhexyl moiety (carbon number of 8) whereas the submission substance has mixed alkyl side chains ranging in carbon backbone length from C11-C13. Because of the similarity in structure and physicochemical properties, it is reasonable to rely on the available data on DEHT to characterize the human health effects of the submission substance.

 

Due to its higher molecular weight and bulkier side chains, the submission substance is expected to demonstrate a lower order of toxicity than DEHT. This is supported by similar structural activity relationships observed with ortho-phthalate ester compounds, i.e. the higher molecular weight phthalates (ester side chains >C7) are less active than the transitional phthalates (ester side chains C4-C6). Thus the use of DEHT to represent the potential hazards of the substance to be registered is considered a conservative estimate of toxicity.

 

The chemical structures of terephthalates (e.g. DEHT and MCP1440) are isomeric to the ortho-phthalates (e.g. DEHP, DINP, and DIDP). That is terephthalates are derived from a 1,4-benzenedicarboxylic acid whereas ortho-phthalates are derived from 1,2-benzenedicarboxylic acid. This structural difference is thought to be very important as it provides the basis for the different metabolic profiles and therefore different toxicity outcomes following exposure to these phthalate esters (Barber, 1994a). Current data suggest that the mono-phthalate (MEHP) is the metabolite responsible for several of the toxicological effects following exposure to DEHP as well as other ortho-phthalates (Ruddick et al., 1981; Mitchell et al., 1985; Price et al., 1991). The distinct decrease in the amount of mono-phthalate formation following exposure to DEHT (and other terephthalates) is believed to account for the decreased toxicity associated with exposure in laboratory animals.